tbuckley/cabot-search huggingface dataset:
Resistance to Selective FGFR Inhibitors in <i>FGFR-</i>Driven Urothelial Cancer
Authors: Francesco Facchinetti, Antoine Hollebecque, Floriane Braye, Damien Vasseur, Yoann Pradat, Rastislav Bahleda, Cédric Pobel, Ludovic Bigot, Olivier Déas, Juan David Florez Arango, Giorgia Guaitoli, Hayato Mizuta, David Combarel, Lambros Tselikas, Stefan Michiels, Sergey I. Nikolaev, Jean-Yves Scoazec, Santiago Ponce-Aix, Benjamin Besse, Ken A. Olaussen, Yohann Loriot, Luc Friboulet
Journal: Cancer Discovery (2023)

Abstract Several fibroblast growth factor receptor (FGFR) inhibitors are approved or in clinical development for the treatment of FGFR-driven urothelial cancer, and molecular mechanisms of resistance leading to patient relapses have not been fully explored. We identified 21 patients with FGFR-driven urothelial cancer treated with selective FGFR inhibitors and analyzed postprogression tissue and/or circulating tumor DNA (ctDNA). We detected single mutations in the FGFR tyrosine kinase domain in seven (33%) patients (FGFR3 N540K, V553L/M, V555L/M, E587Q; FGFR2 L551F) and multiple mutations in one (5%) case (FGFR3 N540K, V555L, and L608V). Using Ba/F3 cells, we defined their spectrum of resistance/sensitivity to multiple selective FGFR inhibitors. Eleven (52%) patients harbored alterations in the PI3K–mTOR pathway (n = 4 TSC1/2, n = 4 PIK3CA, n = 1 TSC1 and PIK3CA, n = 1 NF2, n = 1 PTEN). In patient-derived models, erdafitinib was synergistic with pictilisib in the presence of PIK3CA E545K, whereas erdafitinib–gefitinib combination was able to overcome bypass resistance mediated by EGFR activation. Significance: In the largest study on the topic thus far, we detected a high frequency of FGFR kinase domain mutations responsible for resistance to FGFR inhibitors in urothelial cancer. Off-target resistance mechanisms involved primarily the PI3K–mTOR pathway. Our findings provide preclinical evidence sustaining combinatorial treatment strategies to overcome bypass resistance. See related commentary by Tripathi et al., p. 1964. This article is featured in Selected Articles from This Issue, p. 1949
Learning Curves of Minimally Invasive Distal Pancreatectomy in Experienced Pancreatic Centers
Authors: Sanne Lof, Linda Claassen, Gerjon Hannink, Bilal Al-Sarireh, Bergthor Björnsson, Ugo Boggi, Fernando Burdio, Giovanni Butturini, Giovanni Capretti, Riccardo Casadei, Safi Dokmak, Bjørn Edwin, Alessandro Esposito, Jean M. Fabre, Giovanni Ferrari, Asmund A. Fretland, Fadhel S. Ftériche, Giuseppe K. Fusai, Alessandro Giardino, Bas Groot Koerkamp, Mathieu D’Hondt, Asif Jah, Sivesh K. Kamarajah, Emanuele F. Kauffmann, Tobias Keck, Stijn van Laarhoven, Alberto Manzoni, Marco V. Marino, Ravi Marudanayagam, Izaak Q. Molenaar, Patrick Pessaux, Edoardo Rosso, Roberto Salvia, Zahir Soonawalla, Regis Souche, Steven White, Frans van Workum, Alessandro Zerbi, Camiel Rosman, Martijn W. J. Stommel, Mohammed Abu Hilal, Marc G. Besselink, Coen van Dam, Daniele Ferraro, Jeremy French, Isabella Frigerio, Cristians A Gonzalez, Mohammed Hammoda, Rugved Kulkarni, Michele Mazzola, Niccolò Napoli, Matteo de Pastena, Claudio Ricci, Gianluca Rompianesi, Mushegh A. Sahakyan, Robert Sutcliffe, Tole Tholfson, Patricia Sanchez-Velazquez, Ulrich Wellner
Journal: JAMA Surgery (2023)

Understanding the learning curve of a new complex surgical technique helps to reduce potential patient harm. Current series on the learning curve of minimally invasive distal pancreatectomy (MIDP) are mostly small, single-center series, thus providing limited data.
Nutritional Supplements and Hair Loss—Limitations to the Interpretation of Clinical Studies Before Implementation in Clinical Practice—Reply
Authors: Lara Drake, Kathie Huang, Arash Mostaghimi
Journal: JAMA Dermatology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
A Step Toward Language Equity Using Clinical Trials
Authors: Gregory L. Peck, Benjamin G. Allar, Gezzer Ortega
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
MFN2 suppresses clear cell renal cell carcinoma progression by modulating mitochondria‐dependent dephosphorylation of EGFR
Authors: Li Luo, Denghui Wei, Yihui Pan, Qiu‐Xia Wang, Jian‐Xiong Feng, Bing Yu, Tiebang Kang, Junhang Luo, Jiefeng Yang, Song Gao
Journal: Cancer Communications (2023)

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most lethal renal cancer. An overwhelming increase of patients experience tumor progression and unfavorable prognosis. However, the molecular events underlying ccRCC tumorigenesis and metastasis remain unclear. Therefore, uncovering the underlying mechanisms will pave the way for developing novel therapeutic targets for ccRCC. In this study, we sought to investigate the role of mitofusin‐2 (MFN2) in supressing ccRCC tumorigenesis and metastasis. Methods The expression pattern and clinical significance of MFN2 in ccRCC were analyzed by using the Cancer Genome Atlas datasets and samples from our independent ccRCC cohort. Both in vitro and in vivo experiments, including cell proliferation, xenograft mouse models and transgenic mouse model, were used to determine the role of MFN2 in regulating the malignant behaviors of ccRCC. RNA‐sequencing, mass spectrum analysis, co‐immunoprecipitation, bio‐layer interferometry and immunofluorescence were employed to elucidate the molecular mechanisms for the tumor‐supressing role of MFN2. Results we reported a tumor‐suppressing pathway in ccRCC, characterized by mitochondria‐dependent inactivation of epidermal growth factor receptor (EGFR) signaling. This process was mediated by the outer mitochondrial membrane (OMM) protein MFN2. MFN2 was down‐regulated in ccRCC and associated with favorable prognosis of ccRCC patients. in vivo and in vitro assays demonstrated that MFN2 inhibited ccRCC tumor growth and metastasis by suppressing the EGFR signaling pathway. In a kidney‐specific knockout mouse model, loss of MFN2 led to EGFR pathway activation and malignant lesions in kidney. Mechanistically, MFN2 preferably binded small GTPase Rab21 in its GTP‐loading form, which was colocalized with endocytosed EGFR in ccRCC cells. Through this EGFR‐Rab21‐MFN2 interaction, endocytosed EGFR was docked to mitochondria and subsequently dephosphorylated by the OMM‐residing tyrosine‐protein phosphatase receptor type J (PTPRJ). Conclusions Our findings uncover an important non‐canonical mitochondria‐dependent pathway regulating EGFR signaling by the Rab21‐MFN2‐PTPRJ axis, which contributes to the development of novel therapeutic strategies for ccRCC.
Potential Limitations for Assessing the Association of Whole Blood With Survival in Patients With Severe Hemorrhage
Authors: Chia-Hao Hsu, Chung-Hwan Chen, Pei-Hsi Chou
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
<i>Drosophila</i> Screening Identifies Dual Inhibition of MEK and AURKB as an Effective Therapy for Pancreatic Ductal Adenocarcinoma
Authors: Sho Sekiya, Junki Fukuda, Ryodai Yamamura, Takako Ooshio, Yusuke Satoh, Shinya Kosuge, Reo Sato, Kanako C. Hatanaka, Yutaka Hatanaka, Tomoko Mitsuhashi, Toru Nakamura, Yoshihiro Matsuno, Satoshi Hirano, Masahiro Sonoshita
Journal: Cancer Research (2023)

Abstract Significant progress has been made in understanding the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) by generating and using murine models. To accelerate drug discovery by identifying novel therapeutic targets on a systemic level, here we generated a Drosophila model mimicking the genetic signature in PDAC (KRAS, TP53, CDKN2A, and SMAD4 alterations), which is associated with the worst prognosis in patients. The ‘4-hit’ flies displayed epithelial transformation and decreased survival. Comprehensive genetic screening of their entire kinome revealed kinases including MEK and AURKB as therapeutic targets. Consistently, a combination of the MEK inhibitor trametinib and the AURKB inhibitor BI-831266 suppressed the growth of human PDAC xenografts in mice. In patients with PDAC, the activity of AURKB was associated with poor prognosis. This fly-based platform provides an efficient whole-body approach that complements current methods for identifying therapeutic targets in PDAC. Significance: Development of a Drosophila model mimicking genetic alterations in human pancreatic ductal adenocarcinoma provides a tool for genetic screening that identifies MEK and AURKB inhibition as a potential treatment strategy.
The Surgeon, the Center, and the System—Several Styles to Stage Mastery
Authors: Melissa E. Hogg
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Most People Experiencing More Days of Heavy Wildfire Smoke
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma
Authors: Juyeun Lee, Michael Nicosia, Ellen S. Hong, Daniel J. Silver, Cathy Li, Defne Bayik, Dionysios C. Watson, Adam Lauko, Kristen E. Kay, Sabrina Z. Wang, Sadie Johnson, Mary McGraw, Matthew M. Grabowski, Danielle D. Kish, Amar B. Desai, Wendy A. Goodman, Scott J. Cameron, Hideho Okada, Anna Valujskikh, Robert L. Fairchild, Manmeet S. Ahluwalia, Justin D. Lathia
Journal: Cancer Discovery (2023)

Abstract Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, and emerging evidence suggests that these extend to genetic/epigenetic and cellular differences, including immune responses. However, the mechanisms driving immunologic sex differences are not fully understood. Here, we demonstrate that T cells play a critical role in driving GBM sex differences. Male mice exhibited accelerated tumor growth, with decreased frequency and increased exhaustion of CD8+ T cells in the tumor. Furthermore, a higher frequency of progenitor exhausted T cells was found in males, with improved responsiveness to anti–PD-1 treatment. Moreover, increased T-cell exhaustion was observed in male GBM patients. Bone marrow chimera and adoptive transfer models indicated that T cell–mediated tumor control was predominantly regulated in a cell-intrinsic manner, partially mediated by the X chromosome inactivation escape gene Kdm6a. These findings demonstrate that sex-biased predetermined behavior of T cells is critical for inducing sex differences in GBM progression and immunotherapy response. Significance: Immunotherapies in patients with GBM have been unsuccessful due to a variety of factors, including the highly immunosuppressive tumor microenvironment in GBM. This study demonstrates that sex-biased T-cell behaviors are predominantly intrinsically regulated, further suggesting sex-specific approaches can be leveraged to potentially improve the therapeutic efficacy of immunotherapy in GBM. See related commentary by Alspach, p. 1966. This article is featured in Selected Articles from This Issue, p. 1949
Comments on the myPACE Randomized Clinical Trial
Authors: Daniele Rodolico, Gabriele G. Schiattarella
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Circumferential Pulmonary Vein Isolation With vs Without Additional Low-Voltage-Area Ablation in Older Patients With Paroxysmal Atrial Fibrillation
Authors: Hongwu Chen, Chengzong Li, Bing Han, Fangyi Xiao, Fu Yi, Youquan Wei, Chenyang Jiang, Cao Zou, Linsheng Shi, Wei Ma, Weiming Wang, Yuegang Wang, Hong Du, Long Chen, Minglong Chen, Minglong Chen, Bing Han, Chenyang Jiang, Weizhu Ju, Gang Yang, Zidun Wang, Hao Yang, Jinfeng Wang, Ping Fang, Zhirong Wang, Chaoqun Zhang, Fei Li, Xiaoli Chen, Jianfei Huang, Chenhui Tai, Jie Hao, Yihe Chen, Shengjie Wu, Tingbo Jiang, Yuzhen Zhang, Mingsheng Hu, Jie Li, Miaoyang Hu, Shijie Li, Weidong Li, Xianjin Li, Ling Yang, Lishang Zhai, Xiaoqing Wang, Qiang Liu, Lu Yu, Ruhong Jiang, Shiquan Chen, Shaobo Fan, Fan Zhang, Jianyong Li, Xinzhong Li, Yaowu Liu, Genshan Ma, Mingfang Li, Youmei Shen, Chang Cui, Hailei Liu, Cheng Cai, Xiaohong Jiang, Nan Wu, Xingxing Sun, Qing Yan, Kexin Wang, Wenxi Wu, Fumin Zhang, Xin Yao, Hao Yu, Xiuqing Wang, Zhibin Lu, Lichun Wang, Jiang Cao
Journal: JAMA Cardiology (2023)

The overall success rate of circumferential pulmonary vein isolation (CPVI) treatment in patients with paroxysmal atrial fibrillation (AF) remains suboptimal, especially in older patients.
Allergen-specific IgG4 increase in atopic dermatitis with long-term dupilumab use
Authors: Mariko Ogawa-Momohara, Yoshinao Muro, Chiaki Murase, Tomoki Taki, Kana Tanahashi, Yuta Yamashita, Haruka Koizumi, Ryo Fukaura, Takuya Takeichi, Masashi Akiyama
Journal: British Journal of Dermatology (2023)

This small-scale prospective study investigated the changes in antigen-specific IgG4 (sIgG4) that occur during long-term dupilumab treatment in patients with atopic dermatitis. While dupilumab has been reported to have an inhibitory effect on B-cell maturation, the increase in sIgG4 during dupilumab treatment may indicate that dupilumab indirectly improves allergies in those predisposed to them. We present the possibility of a new therapeutic effect of long-term dupilumab use.
Management of Postpartum Left Main Spontaneous Coronary Artery Dissection
Authors: Chayakrit Krittanawong, Michael J. Attubato, Lori Vales Lay
Journal: JAMA Cardiology (2023)

A woman in her early 40s who was 11 weeks post partum presented with acute pleuritic chest pain, shortness of breath, and nausea that started several hours after arriving on a flight.
Effect of Early Glycemic Control in Youth-Onset Type 2 Diabetes on Longer-Term Glycemic Control and β-Cell Function: Results From the TODAY Study
Authors: Kristen J. Nadeau, Laure El ghormli, Silva Arslanian, Fida Bacha, Sonia Caprio, Christine Chan, Lily C. Chao, Maria Rayas, Maggie K. Siska, Philip Zeitler
Journal: Diabetes Care (2023)

Little is known about the impact of early attainment of tight glycemic control on long-term β-cell function and glycemic control in youth-onset type 2 diabetes. We examined the effect of the initial 6 months of glycemic control on β-cell function and glycemic control longitudinally over 9 years and the impact of sex, race/ethnicity, and BMI on these relationships in adolescents with youth-onset type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.
Health Care Costs Will Comprise About 20% of US Economy by 2031
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal